ELECTROPHYSIOLOGIC IN-VITRO EFFECTS OF COCAINE AND ITS METABOLITES

We studied the in-vitro electrophysiologic effects of equimolar concen trations of cocaine and its metabolites on rat cardiac tissues. The ef fects on the sinus node rate were studied in spontaneously active sino atrial preparations. The order of magnitude of the effects was: ethylc ocaine > cocaine > benzoylecgonine and ecgonine methyl ester > ecgonin e. The effects of cocaine and ethylcocaine were not additive. The acti ons of cocaine and ethylcocaine on membrane potentials were studied in papillary muscles driven at 5 Hz. Both compounds depressed to similar degrees the resting potential and the amplitude of the action potenti al, and increased the duration of the action potential. Simultaneous e xposure to the two drugs did not result in effects greater than those of ethylcocaine or cocaine alone. It is concluded that (a) cocaine and its metabolites depressed the sinus node rate. Only cocaine and ethyl cocaine exerted actions that may be of clinical significance. (b) Ethy lcocaine had an effect greater than that of cocaine on the sinus node rate, and similar to that of the parent compound on ventricular membra ne potentials. Thus, ethylcocaine may play a significant role in the c ardiac electrophysiologic actions of cocaine, when the latter is used in combination with ethanol. (c) The effects of cocaine and ethylcocai ne were not additive.